Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34(+) Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia

This study tested whether circulatory endothelial progenitor cells (EPCs) derived from peripheral arterial occlusive disease (PAOD) patients after receiving combined autologous CD34+ cell and hyperbaric oxygen (HBO) therapy (defined as rejuvenated EPCs) would salvage nude mouse limbs against critica...

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Autores principales: Chen, Yin-Chia, Sheu, Jiunn-Jye, Chiang, John Y., Shao, Pei-Lin, Wu, Shun-Cheng, Sung, Pei-Hsun, Li, Yi-Chen, Chen, Yi-Ling, Huang, Tien-Hung, Chen, Kuan-Hung, Yip, Hon-Kan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660611/
https://www.ncbi.nlm.nih.gov/pubmed/33114267
http://dx.doi.org/10.3390/ijms21217887
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author Chen, Yin-Chia
Sheu, Jiunn-Jye
Chiang, John Y.
Shao, Pei-Lin
Wu, Shun-Cheng
Sung, Pei-Hsun
Li, Yi-Chen
Chen, Yi-Ling
Huang, Tien-Hung
Chen, Kuan-Hung
Yip, Hon-Kan
author_facet Chen, Yin-Chia
Sheu, Jiunn-Jye
Chiang, John Y.
Shao, Pei-Lin
Wu, Shun-Cheng
Sung, Pei-Hsun
Li, Yi-Chen
Chen, Yi-Ling
Huang, Tien-Hung
Chen, Kuan-Hung
Yip, Hon-Kan
author_sort Chen, Yin-Chia
collection PubMed
description This study tested whether circulatory endothelial progenitor cells (EPCs) derived from peripheral arterial occlusive disease (PAOD) patients after receiving combined autologous CD34+ cell and hyperbaric oxygen (HBO) therapy (defined as rejuvenated EPCs) would salvage nude mouse limbs against critical limb ischemia (CLI). Adult-male nude mice (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 (CLI-EPCs (6 × 10(5)) derived from PAOD patient’s circulatory blood prior to CD34(+) cell and HBO treatment (EPC(Pr-T)) by intramuscular injection at 3 h after CLI induction) and group 4 (CLI-EPCs (6 × 10(5)) derived from PAOD patient’s circulatory blood after CD34(+) cell and HBO treatment (EPC(Af-T)) by the identical injection method). By 2, 7 and 14 days after the CLI procedure, the ischemic to normal blood flow (INBF) ratio was highest in group 1, lowest in group 2 and significantly lower in group 4 than in group 3 (p < 0.0001). The protein levels of endothelial functional integrity (CD31/von Willebrand factor (vWF)/endothelial nitric-oxide synthase (eNOS)) expressed a similar pattern to that of INBF. In contrast, apoptotic/mitochondrial-damaged (mitochondrial-Bax/caspase-3/PARP/cytosolic-cytochrome-C) biomarkers and fibrosis (Smad3/TGF-ß) exhibited an opposite pattern, whereas the protein expressions of anti-fibrosis (Smad1/5 and BMP-2) and mitochondrial integrity (mitochondrial-cytochrome-C) showed an identical pattern of INBF (all p < 0.0001). The protein expressions of angiogenesis biomarkers (VEGF/SDF-1α/HIF-1α) were progressively increased from groups 1 to 3 (all p < 0.0010). The number of small vessels and endothelial cell surface markers (CD31(+)/vWF(+)) in the CLI area displayed an identical pattern of INBF (all p < 0.0001). CLI automatic amputation was higher in group 2 than in other groups (all p < 0.001). In conclusion, EPCs from HBO-C34+ cell therapy significantly restored the blood flow and salvaged the CLI in nude mice.
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spelling pubmed-76606112020-11-13 Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34(+) Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia Chen, Yin-Chia Sheu, Jiunn-Jye Chiang, John Y. Shao, Pei-Lin Wu, Shun-Cheng Sung, Pei-Hsun Li, Yi-Chen Chen, Yi-Ling Huang, Tien-Hung Chen, Kuan-Hung Yip, Hon-Kan Int J Mol Sci Article This study tested whether circulatory endothelial progenitor cells (EPCs) derived from peripheral arterial occlusive disease (PAOD) patients after receiving combined autologous CD34+ cell and hyperbaric oxygen (HBO) therapy (defined as rejuvenated EPCs) would salvage nude mouse limbs against critical limb ischemia (CLI). Adult-male nude mice (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 (CLI-EPCs (6 × 10(5)) derived from PAOD patient’s circulatory blood prior to CD34(+) cell and HBO treatment (EPC(Pr-T)) by intramuscular injection at 3 h after CLI induction) and group 4 (CLI-EPCs (6 × 10(5)) derived from PAOD patient’s circulatory blood after CD34(+) cell and HBO treatment (EPC(Af-T)) by the identical injection method). By 2, 7 and 14 days after the CLI procedure, the ischemic to normal blood flow (INBF) ratio was highest in group 1, lowest in group 2 and significantly lower in group 4 than in group 3 (p < 0.0001). The protein levels of endothelial functional integrity (CD31/von Willebrand factor (vWF)/endothelial nitric-oxide synthase (eNOS)) expressed a similar pattern to that of INBF. In contrast, apoptotic/mitochondrial-damaged (mitochondrial-Bax/caspase-3/PARP/cytosolic-cytochrome-C) biomarkers and fibrosis (Smad3/TGF-ß) exhibited an opposite pattern, whereas the protein expressions of anti-fibrosis (Smad1/5 and BMP-2) and mitochondrial integrity (mitochondrial-cytochrome-C) showed an identical pattern of INBF (all p < 0.0001). The protein expressions of angiogenesis biomarkers (VEGF/SDF-1α/HIF-1α) were progressively increased from groups 1 to 3 (all p < 0.0010). The number of small vessels and endothelial cell surface markers (CD31(+)/vWF(+)) in the CLI area displayed an identical pattern of INBF (all p < 0.0001). CLI automatic amputation was higher in group 2 than in other groups (all p < 0.001). In conclusion, EPCs from HBO-C34+ cell therapy significantly restored the blood flow and salvaged the CLI in nude mice. MDPI 2020-10-23 /pmc/articles/PMC7660611/ /pubmed/33114267 http://dx.doi.org/10.3390/ijms21217887 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Yin-Chia
Sheu, Jiunn-Jye
Chiang, John Y.
Shao, Pei-Lin
Wu, Shun-Cheng
Sung, Pei-Hsun
Li, Yi-Chen
Chen, Yi-Ling
Huang, Tien-Hung
Chen, Kuan-Hung
Yip, Hon-Kan
Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34(+) Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia
title Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34(+) Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia
title_full Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34(+) Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia
title_fullStr Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34(+) Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia
title_full_unstemmed Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34(+) Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia
title_short Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34(+) Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia
title_sort circulatory rejuvenated epcs derived from paod patients treated by cd34(+) cells and hyperbaric oxygen therapy salvaged the nude mouse limb against critical ischemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660611/
https://www.ncbi.nlm.nih.gov/pubmed/33114267
http://dx.doi.org/10.3390/ijms21217887
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